We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

28 January 2018

The impairment of the ubiquitin-proteasome system (UPS) is thought to be an early event in neurodegeneration, and monitoring UPS alterations might serve as a disease biomarker. Our aim was to establish an alternate method to antibody-based assays for the selective measurement of free monoubiquitin in cerebrospinal fluid (CSF). Free monoubiquitin was measured with liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MS/MS) in CSF of patients with Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), behavioral variant of frontotemporal dementia (bvFTD), Creutzfeldt-Jakob disease (CJD), Parkinson's disease (PD), primary progressive aphasia (PPA), and progressive supranuclear palsy (PSP). The LC-MS/MS method showed excellent intra- and interassay precision (4.4-7.4% and 4.9-10.3%) and accuracy (100-107% and 100-106%). CSF ubiquitin concentration was increased compared with that of controls (33.0 ± 9.7 ng/mL) in AD (47.5 ± 13.1 ng/mL, p < 0.05) and CJD patients (171.5 ± 103.5 ng/mL, p < 0.001) but not in other neurodegenerative diseases. Receiver operating characteristic curve (ROC) analysis of AD vs control patients revealed an area under the curve (AUC) of 0.832, and the specificity and sensitivity were 75 and 75%, respectively. ROC analysis of AD and FTLD patients yielded an AUC of 0.776, and the specificity and sensitivity were 53 and 100%, respectively. In conclusion, our LC-MS/MS method may facilitate ubiquitin determination to a broader community and might help to discriminate AD, CJD, and FTLD patients.

9 January 2018

Stroke recovery research involves distinct biological and clinical targets compared to the study of acute stroke. Guidelines are proposed for the pre-clinical modeling of stroke recovery and for the alignment of pre-clinical studies to clinical trials in stroke recovery.

29 December 2017

Imagery plays an important role in our life. Motor imagery is the mental simulation of a motor act without overt motor output. Previous studies have documented the effect of motor imagery practice. However, its translational potential for patients as well as for athletes, musicians and other groups, depends largely on the transfer from mental practice to overt physical performance. We used bilateral transcranial direct current stimulation (tDCS) over sensorimotor areas to modulate neural lateralization patterns induced by unilateral mental motor imagery and the performance of a physical motor task. Twenty-six healthy older adults participated (mean age = 67.1 years) in a double-blind cross-over sham-controlled study. We found stimulation-related changes at the neural and behavioural level, which were polarity-dependent. Specifically, for the hand contralateral to the anode, electroencephalographic activity induced by motor imagery was more lateralized and motor performance improved. In contrast, for the hand contralateral to the cathode, hemispheric lateralization was reduced. The stimulation-related increase and decrease in neural lateralization were negatively related. Further, the degree of stimulation-related change in neural lateralization correlated with the stimulation-related change on behavioural level. These convergent neurophysiological and behavioural effects underline the potential of tDCS to improve mental and physical motor performance.

16 February 2018

OBJECTIVES: Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy. METHODS: High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy. RESULTS: All patients responded well to treatment (46% mean improvement off medication UPDRS-III [p < 0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = -10(-9.5), Y = -13(-1) and Z = -7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity. INTERPRETATION: These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.

16 February 2018

Diffusion MRI allows us to make inferences on the structural organisation of the brain by mapping water diffusion to white matter microstructure. However, such a mapping is generally ill-defined; for instance, diffusion measurements are antipodally symmetric (diffusion along x and -x are equal), whereas the distribution of fibre orientations within a voxel is generally not symmetric. Therefore, different sub-voxel patterns such as crossing, fanning, or sharp bending, cannot be distinguished by fitting a voxel-wise model to the signal. However, asymmetric fibre patterns can potentially be distinguished once spatial information from neighbouring voxels is taken into account. We propose a neighbourhood-constrained spherical deconvolution approach that is capable of inferring asymmetric fibre orientation distributions (A-fods). Importantly, we further design and implement a tractography algorithm that utilises the estimated A-fods, since the commonly used streamline tractography paradigm cannot directly take advantage of the new information. We assess performance using ultra-high resolution histology data where we can compare true orientation distributions against sub-voxel fibre patterns estimated from down-sampled data. Finally, we explore the benefits of A-fods-based tractography using in vivo data by evaluating agreement of tractography predictions with connectivity estimates made using different in-vivo modalities. The proposed approach can reliably estimate complex fibre patterns such as sharp bending and fanning, which voxel-wise approaches cannot estimate. Moreover, histology-based and in-vivo results show that the new framework allows more accurate tractography and reconstruction of maps quantifying (symmetric and asymmetric) fibre complexity.

19 February 2018

Activity in anterior cingulate cortex (ACC) has been linked both to commitment to a course of action, even when it is associated with costs, and to exploring or searching for alternative courses of action. Here we review evidence that this is due to the presence of multiple signals in ACC reflecting the updating of beliefs and internal models of the environment and encoding aspects of choice value, including the average value of choices afforded by the environment ('search value'). We contrast this evidence with the influential view that ACC activity is better described as reflecting task difficulty. A consideration of cortical neural network properties explains why ACC may carry such signals and also exhibit sensitivity to task difficulty.

24 March 2017

19 May 2016

Using aspirin urgently could substantially reduce the risk of major strokes in patients who have minor ‘warning’ events, a group of European researchers led by Peter Rothwell has found. Writing in the Lancet, the team say that immediate self-treatment when patients experience stroke-like symptoms would considerably reduce the risk of major stroke over the next few days.

10 June 2015

10 June 2015

10 June 2015

10 June 2015

21 August 2015

We are looking to recruit DPhil students to undertake research in the laboratory starting October 2016. Please get in touch if you may be interested. Deadlines for application are early, so we recommend that you get in touch during Autumn 2015.

6 January 2017

16 January 2017

A Phase 2 RCT of intracerebroventricular administration of platelet-derived growth factor (pdGF) in PD. One of 5 European centres involved in the EU funded FP7 project. The Principal Investigators are Mr Alex Green and Dr Marko Bogdanovich.

This group, led by Professor Peter Brown, investigates the pathophysiology of Parkinson's disease, with the goal of developing new interventional treatments. It is funded by Parkinson's UK, the Medical Research Council, National Institute of Research Oxford Biomedical Centre and Rosetrees Trust.

This group, led by Professor Masud Husain, works to understand and treat disorders of attention, memory, decision-making and motivation in patients with Parkinson’s disease, atypical Parkinsonian and other movement disorders. Research is supported by the Wellcome Trust, with clinics at the John Radcliffe and central Oxford.

This group, led by Associate Professor George Tofaris, aims to understand fundamental biological processes that could inform the development of targeted therapies in neurodegenerative and neurogenetic disorders.

16 August 2013

Our work focuses on translating imaging analysis methods to better understand processes such as brain maturation and ageing, and with a particular emphasis on neurodegenerative disorders (Alzheimer's, Parkinson's, Huntington's, ALS).

15 January 2013

Our group investigates the role of risk factors in the development of multiple sclerosis through functional genetic and neuro-immunological analyses, with the aim of translating these findings into a clinical utility.

15 January 2013

Our group aims to deliver the highest quality translational and clinical research within both investigator- and commercial-led clinical trials with a focus on relieving the disease burden of MS to patients and their carers.

15 January 2013

We explore the neuropathology of multiple sclerosis and other inflammatory and neurodegenerative diseases using a multidisciplinary team approach to post-mortem brain and spinal cord tissue. The aim is that the understanding derived from these studies will translate into ideas for improved treatments for living patients.